Linoleic acid is a major component of triglyceride stores in endothelial cells and can be oxidized by several enzymes. Leukotoxin (9,10-epoxy-12-octadecenoate, LTX), an epoxide metabolite of linoleic acid, was found in lung lavage fluid obtained from adult respiratory distress syndrome (ARDS) patients. Clinically, LTX has been associated with ARDS. Recently, we found that leukotoxin-diol (LTXD), the hydrated product of LTX, is more toxic than the parent compound LTX to alveolar type II cells in vitro. To establish whether this difference in the toxicity of LTX and LTXD exists in vivo, Swiss Webster mice were intravenously administered LTX or LTXD (400 mg/kg). The mice treated with LTXD died of ARDS-like respiratory distress in 5 minutes, while the animals survived the LTX exposure. Histopathologic evaluation of the lungs revealed massive alveolar edema and hemorrhage with interstitial edema around blood vessels in lungs of mice treated with LTXD. Compared to carrier treated controls, lungs of mice treated with LTX had peribronchiolar and perivascular edema, but little change in alveolar spaces. We conclude LTXD is more toxic to the lung than LTX in vivo. These in vivo studies demonstrated further evidence that leukotoxin may act as a pro-toxicant which is converted to the corresponding diol producing cytotoxic effects. (Chemical Equation Presented).
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology